The invention relates to systems, devices, kits, compositions, and methods for detecting toxicants, pathogens, and biomarkers in a biological sample. The systems, devices, kits, compositions, and methods may be utilized safely to collect, process, and transport biological samples, such as a dried blood sample from a skin prick, to a reference laboratory.
Toxicants, such as heavy metals including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), are ubiquitous environmental toxicants. In fact, As, Pb, Hg, and Cd are listed as the 1st, 2nd, 3rd, and 7th most important hazardous substances on the 2011 CERCLA priority list of 275 substances, respectively. Exposure to heavy metals can occur through a variety of exposure routes, including inhalation as dust and fumes, and ingestion from food and water, and can cause a wide spectrum of health problems including convulsions, coma, renal failure, injuries to the lungs and neurologic system, memory loss, delirium, diabetes, kidney damage, and a variety of cancers.
Currently the “gold standard” for quantifying heavy metals in blood is to use whole blood collected by venipuncture. Because venous blood collection is costly, invasive, and must be performed by a trained phlebotomist, these obstacles constrain screening efforts for assessing exposure to toxic metals in non-clinical settings. In addition, heavy metals such as lead are routinely measured in clinical settings in younger children, often as part of state mandated screening programs to assess environmental exposures. Younger children are more difficult to phlebotomize. Given the draw backs of venipuncture based methods, a dried blood sample approach using simple and minimally invasive methods (e.g., based on a finger prick or heel prick) has large advantages for both population based surveys, public health surveillance, and standard clinical testing.
Newborn Screening (NS) for detection of inherited or prenatally acquired diseases is a routine aspect of newborn care in all developed nations. NS utilizes unsealed, air-dried filter paper dried blood spot (DBS) paper “cards” that contain sensitive personal and private information as to the patient and his/her parents, as well as blood specimens, usually obtained by heelstick, for laboratory analysis.
The most common filter paper used to collect newborn DBS samples is Whatman #903 Protein Saver Cards. However, while Whatman #903 filter paper and filter paper in general have been rigorously tested and optimized for measuring a variety of biomarkers, they are not designed for collecting blood samples and performing trace level heavy metals analysis. This is at least partially because background contamination in the filter paper (e.g., at ppb) interferes with quantification of heavy metals in DBS samples and can lead to imprecise estimates of exposure.
An additional challenge for quantifying biomarkers in DBS samples is the unknown volume of blood in each sample. DBS are generally collected via a simple finger or heel prick, and as a result, the volume of blood applied to the filter paper is unknown. The common convention for determining blood volume is to take a standard punch from the blood spot (typically 3-6 mm in diameter) and estimating the blood volume based on the size of the punch. However, these crude approximations result in too much measurement error for the precise quantification of heavy metals, which are present in very small quantities (e.g., at ppb).
In addition to toxicants, infectious diseases are a leading cause of death, disability, suffering, and medical expense among newborns and children worldwide. Epidemics of novel, often potentially fatal, illnesses such as MERS, Avian Flu, Ebola, Zika are being recognized with ever-greater frequency worldwide as population mobility and density increases globally. The potential for genetic manipulation of known pathogens to increase both transmissibility and virulence remains a national security threat. Blood (or other biological specimes) spotted onto filter paper cards cannot presently safely be used for analysis of novel potential infection(s) because of uncertainty as to transmission potential, should such cards be allowed to simply air dry and then be shipped by standard ground carrier to reference labs—as is the current situation with Government-sponsored NS programs. In particular, the current DBS NS card is not compatible with the collection of urine for subsequent laboratory analysis. This is a critical current deficit as urine Zika viral loads as quantified by RT PCR are more persistent, and provide better diagnostic information, than blood Zika viral levels. Zika viruria is detectable at low fluid volume.
Here, we disclose systems, devices, kits, compositions, and methods to overcome these problems in the art. The disclosed systems, devices, kits, compositions, and methods may be used safely to collect, transport, and test a biological sample, such as a dried blood sample from a skin prick, for toxicants, such as heavy metals and other toxicants. In addition, the disclosed systems, devices, kits, compositions, and methods may be used safely to collect, transport, and test a biological sample, such as a dried blood sample from a skin prick for pathogens, such as bacterial and viral pathogens, and for biomarkers.